The NCI Chemical Biology Consortium (CBC)-currently under development-will facilitate the discovery and development of new agents to treat cancer. This effort will be managed by the NCI's Experimental Therapeutics Program (NExT) through SAIC-Frederick. It is envisioned that initiation of this consortium will provide cutting-edge chemical tools for probing complex signaling pathways and will serve as the starting point for the elaboration of first-in-class targeted therapies. The mission of the CBC is to increase the flow of early stage drug candidates into NCI's drug development pipeline. The CBC will be an integrated research consortium at the interface of chemical biology and molecular oncology that will, working with various programs within the NCI's Division of Cancer Treatment and Diagnosis (DCTD) and the Center for Cancer Research (CCR), establish an iterative cancer drug discovery group on the scale of a small biotechnology concern.
By establishing a network of chemical biologists and molecular oncologists from government, industry and academia, these CBC associate organizations and the NCI (collectively "Participants") can further address the unmet needs in therapeutic oncology focusing on areas such as "undruggable" targets and under-represented malignancies e.g. pediatric tumors and natural products. Through the CBC and the interactions among the various Participants, the NCI's drug discovery and development pipeline can be enabled from target identification through proof-of-concept (POC) clinical trials. It is expected and understood that NCI will have the option to clinically develop successful compounds (NMEs) created by the CBC. The long-term vision of the CBC is to bridge the gap between basic scientific investigation and clinical research supported by the NCI. This integrated process will allow NCI to maximize the return on its investment in molecular oncology over the past decade by making the following world-class resources available to CBC Participants:
The primary strength of the NCI's drug discovery and development program has been focused upon the transition from early development to first-in-human studies. NCI's current system is highly-efficient at taking late-stage preclinical drug candidates through the final steps of development that lead to a successful IND filing with the Food and Drug Administration (FDA). The core elements for this stage of development are toxicology and production of clinical-grade material. These functions are the most expensive and least available in the academic sector. Furthermore, the NCI's efforts to move agents from late preclinical studies to first-in-human clinical trials have been significantly enhanced over the past three years. The DCTD and the CCR have moved to significantly improve the flow of molecules from intramural and extramural academic investigators into the clinic, as recently exemplified by the ABT-888 Phase 0 trial 1,2. The critical feature of this effort has been the linkage of the molecular pharmacology and early clinical testing resources of the CCR with the extramural resources of DCTD in the areas of screening, imaging, pre-clinical pharmacology and toxicology, and formulation to produce an NCI-led oncologic therapeutics development effort capable of substantively facilitating the clinical testing of novel anticancer molecules.
The NCI has also assembled, and supports, a large set of highly-talented clinical investigators who can launch the initial human evaluation of a new agent with efficiency and skill at the conclusion of preclinical development. For novel molecular entities that have no prior experience in humans, this is an invaluable resource.
Through the establishment of the CBC and the recruitment of the Participants, the NCI experimental therapeutics effort will prioritize its resources to meet the following objectives:
Although the CBC is still in the development process, several public documents are available to provide interested participants with background information about the consortium.
1 1Kummar S, Kinders R, Gutierrez ME, Rubinstein L, Parchment RE, Phillips LR, Ji J, Monks A, Low JA, Chen A, Murgo AJ, Collins J, Steinberg SM, Eliopoulos H, Giranda VL, Gordon G, Helman L, Wiltrout R, Tomaszewski JE, Doroshow JH. Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies. J Clin Oncol. Published online April 13, 2009. 10.1200/JCO.2008.19.7681.
2 Donawho CK, Luo Y, Luo Y, et al. ABT-888, an orally active poly (ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res 2007:13;2728-2737.